WO2010121341A2 - Bioactive composite for bone repair - Google Patents

Bioactive composite for bone repair Download PDF

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Publication number
WO2010121341A2
WO2010121341A2 PCT/BR2010/000144 BR2010000144W WO2010121341A2 WO 2010121341 A2 WO2010121341 A2 WO 2010121341A2 BR 2010000144 W BR2010000144 W BR 2010000144W WO 2010121341 A2 WO2010121341 A2 WO 2010121341A2
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WO
WIPO (PCT)
Prior art keywords
bioactive
composite
bone repair
bone
matrix
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PCT/BR2010/000144
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French (fr)
Portuguese (pt)
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WO2010121341A3 (en
Inventor
Catarine Bezerra Cavalcanti
Nereide Stela Santos MAGALHÃES
José Lamartine de Andrade AGUIAR
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Universidade Federal De Pernambuco - Ufpe
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Priority to PCT/BR2010/000144 priority Critical patent/WO2010121341A2/en
Publication of WO2010121341A2 publication Critical patent/WO2010121341A2/en
Publication of WO2010121341A3 publication Critical patent/WO2010121341A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention applies to the fields of health sciences, pharmacotechnics and biological tissue engineering.
  • the invention relates to bone tissue fixation, filling of critical bone tissue defects, osteoconduction and osteoinduction.
  • the invention applies to the controlled release of drugs and nanodevices.
  • the area of engineering of biological tissues it can be highlighted the use as bone substitutes with function of conduction and tissue induction.
  • the composite was also developed with the purpose of being used as fixation pins of bone tissue lesions or machined in the screw model with the same function and application. Another application is in the form of laminates to correct critical flat bone defects and also as fixation plates.
  • Composites are among the most commonly used materials for bioactive function bone repair in order to accelerate the process of osteoconduction and osteoinduction in the treatment of critical bone tissue defects. They may be derived from organic or inorganic matrices and reinforcements.
  • inorganic composites For matrix and reinforcement composites of inorganic origin, there are no systematic studies of cytotoxicity and biococompatibility. Its usual industrial application is used as packaging materials and components for machines and engines.
  • inorganic composites are bioactive and biocompatible products, specifically bioceramics and glass and titanium derivatives used particularly in dentistry, traumatology and orthopedics.
  • bioactivity and biocompatibility are inorganic derivatives that do not allow remodeling of organic tissues.
  • the organic matrix composites used for biological applications are mostly protein derivatives such as collagen from different animal sources. These products are biologically active and may lead to immune rejection responses.
  • the composites are also the alloys that present resistance and biointegration and are used as fixators and implants. Metal alloys remain in the tissues, are stable but do not allow remodeling.
  • materials for biological application should preferably be non-toxic, biocompatible, with adequate physical and chemical characteristics (good strength, flexibility, elastic deformation and purity) to different tissues and biointegrable inducing remodeling of the implant area.
  • materials for biological application should preferably be non-toxic, biocompatible, with adequate physical and chemical characteristics (good strength, flexibility, elastic deformation and purity) to different tissues and biointegrable inducing remodeling of the implant area.
  • Previous innovations for the same purpose utilizing microbial polysaccharides such as bacterial cellulose, carry out chemical processes by chemical modifications of the cellulose chain by adding functional groups (WO / 2009/039238).
  • the bioactive composite for bone repair presented here differs from what is currently known to be characterized as a product consisting entirely of organic, matrix and inorganic components, reinforcement, which together is bioactive, nontoxic, biocompatible, moldable, resistant, flexible and its obtaining process do not use chemical reactions or baths in solutions. It combines in one product properties of biocompatibility, biointegration and fixation of bone tissue.
  • the invention is a composite whose matrix is a polysaccharide and the reinforcement is a compound of inorganic origin (calcium hydroxide, hydroxyapatite and calcium phosphate).
  • the reinforcement was used to associate a bioactive induction in the composite, specific to bone tissue.
  • the reinforcement was used in different concentrations in relation to the matrix, to obtain composites with rupture resistance and different elastic deformation indices suitable to the specific applications of osteofixation, critical defects filling, osteoinduction, osteoconduction and osteorepation.
  • the reinforcement may be calcium hydroxide, hydroxyapatite or calcium phosphate, or a two to two combination of these in different proportions, or the three reinforcements combined in different proportions may be used.
  • the biopolymer must be emulsified to form the basic matrix at different concentrations for the addition of one of the reinforcements. Dispersion of components should be by agitation. Excess water should be removed which will result in a paste that can be shaped and dehydrated. The resulting mass is a resilient, resilient and elastically deformable composite.
  • the matrix relating to these experiments was of biological origin, composed entirely of sugars and glucuronic acid, organic components found as metabolic actives in living beings, including man.
  • Organic matrix is a polysaccharide consisting of sugars from natural sources that does not elicit an immune response of rejection like protein derivatives.
  • Bacterial expolysaccharide was obtained based on the production process described in PI9603700-8; PI0301912-8 and PI0504376-0.
  • the biopolymer was emulsified from a 1g volume weight suspensions of the biopolymer to 50 to 150mL of water, forming the base matrix at different concentrations for the specific addition of one or combination of reinforcement at concentrations of 0.01 to 3%. relative to the matrix.
  • experiments were performed with calcium hydroxide and calcium phosphate. Dispersion of the components was by continuous stirring for 30 minutes. Excess water was removed by filtration. The resulting paste was modeled by cold extrusion and compression between plates. Then the dough was dehydrated in a particle free environment.
  • the resulting mass is a non-toxic, bioactive, biocompatible, moldable, tear-resistant and elastically deformable composite.
  • the product to which the present invention relates exhibited calcium phosphate deposition on its surface, which is a precursor of hydroxyapatite, an organic material present in 90% of bone tissue.
  • a biodegradable natural product obtained from raw material from renewable sources as apatite-organic polymer composites is an attraction of various methods of manufacturing biomaterials as bone remodeling.
  • the invention relates to the development of a bioactive composite whose polymeric matrix is composed of polysaccharide.
  • As reinforcement calcium derivatives such as calcium hydroxide, apatite hydroxide, calcium phosphate are used to obtain bioactive composites with specificity for bone tissue.
  • the reinforcement was used at different concentrations in relation to the matrix to obtain modelable composites, with resistance to rupture and with different elastic deformation indices suitable to the specific applications of osteofixation, osteorepation, osteoinduction and osteoconduction for the treatment of bone tissue injuries. loss of substance including critical defects.
  • the invention is a composite whose matrix is a polysaccharide and the reinforcement is a compound of inorganic origin (calcium hydroxide, hydroxyapatite and calcium phosphate).
  • the reinforcement was used to associate a bioactive induction in the composite, specific to for bone tissue.
  • the reinforcement was used in different concentrations in relation to the matrix, to obtain composites with rupture resistance and different elastic deformation indices suitable to the specific applications of osteofixation, critical defects filling, osteoinduction, osteoconduction and osteorepation.
  • the biopolymer must be emulsified to form the basic matrix at different concentrations for the addition of one of the reinforcements. Dispersion of components should be by agitation. Excess water should be removed which will result in a paste that can be shaped and dehydrated. The resulting mass is a resilient, resilient and elastically deformable composite.
  • the matrix of these experiments is of biological origin, composed entirely of sugars and glucuronic acid, organic components found as metabolic actives in living beings, including man.
  • Organic matrix is a polysaccharide consisting of sugars from natural sources that does not elicit an immune response of rejection like protein derivatives.
  • Bacterial expolysaccharide was obtained based on the production process described in PI9603700-8; PI0301912-8 and PI0504376-0.
  • the biopolymer was emulsified from a 1g volume weight suspensions of the biopolymer to 50 to 150mL of water, forming the base matrix at different concentrations and the addition of one or the reinforcements or their association at a concentration of 0.01 to 3. , 0% of the matrix.
  • experiments were performed with calcium hydroxide and calcium phosphate. Dispersion of the components was by continuous stirring for 30 minutes. Excess water was removed by filtration. The resulting paste was modeled by cold extrusion and compression between plates. Then the dough was dehydrated in a safe environment with low level of particulate matter. The resulting mass is a non-toxic, bioactive, biocompatible, moldable, tear-resistant and elastically deformable composite.
  • the product to which the present invention relates exhibited calcium phosphate deposition on its surface, which is a precursor of hydroxyapatite, an organic material present in 90% of bone tissue.
  • a natural, biodegradable product obtained from raw materials from renewable sources such as apatite-organic polymer composites is an attraction of various methods of manufacturing biomaterials as bone remodeling.

Abstract

The present invention has applications in the fields of medicine, pharmaceutics and biological tissue engineering. The invention relates to the development of a bioactive composite for bone repair with a polymer matrix composed of a polysaccharide, and strengthened with calcium derivatives, such as calcium hydroxide, hydroxylapatite, or calcium phosphate, in order to produce bioactive composites specific to bone tissue. The strengthening material is used at different concentrations relative to the matrix in order to produce mouldable composites machined into fracture-resistant screws, pins and plates with various elastic deformation values suitable for specific uses in bone fixation, bone repair, bone induction and bone conduction for the treatment of lesions of bone tissue accompanied by loss of substance, including critical defects.

Description

COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS  BIOACTIVE COMPOSITE FOR BONE REPAIR
Campo Field
A presente invenção aplica-se às áreas das ciências da saúde, farmacotecnia e engenharia de tecidos biológicos.  The present invention applies to the fields of health sciences, pharmacotechnics and biological tissue engineering.
Em especial, com relação à área das ciências da saúde, a invenção está relacionada à fixação de tecidos ósseos, preenchimento de defeitos críticos dos tecidos ósseos, osteocondução e osteoindução. Quanto à área de farmacotecnia a invenção aplica-se à liberação controlada de medicamentos e nanodispositivos. Em relação à área de engenharia de tecidos biológicos pode-se ressaltar a utilização como substitutivos ósseos com função de condução e indução de tecido. In particular, with regard to the health sciences area, the invention relates to bone tissue fixation, filling of critical bone tissue defects, osteoconduction and osteoinduction. Regarding the field of pharmacotechnics the invention applies to the controlled release of drugs and nanodevices. Regarding the area of engineering of biological tissues, it can be highlighted the use as bone substitutes with function of conduction and tissue induction.
O compósito foi desenvolvido também com o objetivo de ser utilizado como pinos fixadores de lesões do tecido ósseo ou usinados no modelo de parafusos com a mesma função e aplicação. Outra aplicação é em forma de laminados para correção de defeitos críticos de ossos planos e também como placas fixadoras. The composite was also developed with the purpose of being used as fixation pins of bone tissue lesions or machined in the screw model with the same function and application. Another application is in the form of laminates to correct critical flat bone defects and also as fixation plates.
Anterioridades Priorities
O estado da arte relativo ao pedido possui amplas especificações, direcionadas particularmente a aplicações industriais. Os compósitos estão entre os materiais mais utilizados para fins de reparos ósseos com função bioativa a fim de acelerar o processo de osteocondução e osteoindução no tratamento de defeitos críticos do tecido ósseo. Eles podem ser derivados de matrizes e reforços orgânicos ou inorgânicos. The state-of-the-art application has broad specifications, particularly for industrial applications. Composites are among the most commonly used materials for bioactive function bone repair in order to accelerate the process of osteoconduction and osteoinduction in the treatment of critical bone tissue defects. They may be derived from organic or inorganic matrices and reinforcements.
Para compósitos derivados de matriz e reforço de origem inorgânica, não se encontra estudos sistemáticos de citotoxicidade e biococompatibilidade. A sua aplicação usual é industrial sendo utilizados como materiais para embalagem e componentes para máquinas e motores. Entre os compósitos inorgânicos existem produtos bioativos e biocompativeis, especificamente as biocerâmicas e derivados de vidro e de titânio utilizados particularmente em odontologia, traumatologia e ortopedia. Apesar da bioatividade e biocompatibilidade são derivados inorgânicos que não permite remodelação dos tecidos orgânicos. Os compósitos de matriz orgânica utilizados para aplicações biológicas, na sua maioria são derivados protéicos como o colágeno de diferentes origens animais. Esses produtos são biologicamente ativos e podem levar a respostas imunológicas de rejeição. For matrix and reinforcement composites of inorganic origin, there are no systematic studies of cytotoxicity and biococompatibility. Its usual industrial application is used as packaging materials and components for machines and engines. Among inorganic composites are bioactive and biocompatible products, specifically bioceramics and glass and titanium derivatives used particularly in dentistry, traumatology and orthopedics. Despite bioactivity and biocompatibility are inorganic derivatives that do not allow remodeling of organic tissues. The organic matrix composites used for biological applications are mostly protein derivatives such as collagen from different animal sources. These products are biologically active and may lead to immune rejection responses.
Inúmeros compósitos são apresentados como funcionalmente ativos para a prática de substituição de tecidos particularmente, nas áreas de odontologia, traumatologia e ortopedia. No entanto, não se encontra materiais disponíveis que associem características físicas e químicas (resistência, flexibilidade e deformação elástica adequadas aos diferentes tecidos) indispensáveis para atender as exigências de um substitutivo de tecido. Além disso, tais compósitos não apresentam nem biocompatibilidade, nem baixa citotoxicidade, nem biointeg ração, nem remodelagem da área do implante. Numerous composites are presented as functionally active for the practice of tissue replacement particularly in the areas of dentistry, traumatology and orthopedics. However, there are no materials available that combine physical and chemical characteristics (strength, flexibility and elastic deformation appropriate to different fabrics) indispensable to meet the requirements of a fabric substitute. Moreover, such composites exhibit neither biocompatibility, low cytotoxicity, biointegration, nor implant area remodeling.
Além dos compósitos encontram-se também as ligas metálicas que apresentam resistência e biointegração e são utilizadas como fixadores e implantes. As ligas metálicas permanecem nos tecidos, são estáveis mas, não permitem a remodelação dos mesmos. Besides the composites are also the alloys that present resistance and biointegration and are used as fixators and implants. Metal alloys remain in the tissues, are stable but do not allow remodeling.
Resumindo, os materiais para aplicação biológica devem ser de preferência atóxicos, biocompatível, com características físicas e químicas adequadas (boa resistência, flexibilidade, deformação elástica e pureza) aos diferentes tecidos e biointegrável induzindo a remodelação da área do implante. Não se encontra, até onde se pode pesquisar, materiais que reúnam todas as especificações de um substitutivo de tecido ideal. Inovações anteriores para os mesmos fins, que utilizam polissacarídeos microbianos como a celulose bacteriana, realizam processos químicos por meio de modificações químicas da cadeia de celulose adicionando grupos funcionais (WO/2009/039238). O compósito bioativo para reparos ósseos, apresentado aqui, difere do atualmente conhecido por se caracterizar como um produto constituído integralmente de componentes orgânicos, matriz e inorgânicos, reforço, que em conjunto é bioativo, atóxico, biocompatível, modelável, resistente, flexível e seu processo de obtenção não usar reações químicas nem banhos em soluções. Reúne em um só produto propriedades de biocompatibilidade, biointegração e fixação do tecido ósseo. In short, materials for biological application should preferably be non-toxic, biocompatible, with adequate physical and chemical characteristics (good strength, flexibility, elastic deformation and purity) to different tissues and biointegrable inducing remodeling of the implant area. To the best of your knowledge, you will not find materials that meet all the specifications of an ideal fabric substitute. Previous innovations for the same purpose, utilizing microbial polysaccharides such as bacterial cellulose, carry out chemical processes by chemical modifications of the cellulose chain by adding functional groups (WO / 2009/039238). The bioactive composite for bone repair presented here differs from what is currently known to be characterized as a product consisting entirely of organic, matrix and inorganic components, reinforcement, which together is bioactive, nontoxic, biocompatible, moldable, resistant, flexible and its obtaining process do not use chemical reactions or baths in solutions. It combines in one product properties of biocompatibility, biointegration and fixation of bone tissue.
Problemas e Limitações Problems and Limitations
Inúmeros compósitos são apresentados como funcionalmente ativos para a prática de substituição de tecidos particularmente nas áreas de odontologia, traumatologia e ortopedia. Numerous composites are presented as functionally active for tissue replacement practice particularly in the areas of dentistry, traumatology and orthopedics.
No entanto, não se encontra materiais disponíveis que associem características físicas e químicas indispensáveis para atender as exigências de um substitutivo de tecido: resistência, flexibilidade e deformação elástica adequadas aos diferentes tecidos, além de apresentarem biocompatibilidade, baixa citotoxicidade, ou mesmo, atóxico e apresente biointegração, remodelando a área do implante. Além dos compósitos encontram-se também as ligas metálicas que apresentam resistência e biointegração e são utilizadas como fixadores e implantes. As ligas metálicas permanecem nos tecidos, são estáveis e não permitem a remodelação dos mesmos. Espera-se que os materiais para aplicação biológica sejam atóxicos, biocompatível e atendam as características físicas e químicas como resistência, flexibilidade, deformação elástica e pureza, adequadas aos diferentes tecidos, sofram biointegração induzindo a remodelação da área do implante. Não se encontra materiais que reúnam todas as especificações de um substitutivo de tecido ideal. Os compósitos de matriz orgânica utilizados para aplicações biológicas, na sua maioria são derivados protéicos como o colágeno de diferentes origens animais. Esses produtos são biologicamente ativos podendo levar a respostas imunológicas de rejeição. Solução However, there are no materials available that combine physical and chemical characteristics indispensable to meet the requirements of a fabric substitute: resistance, flexibility and elastic deformation suitable for different fabrics, besides presenting biocompatibility, low cytotoxicity, or even, nontoxic and present. biointegration, reshaping the implant area. Besides the composites are also the alloys that present resistance and biointegration and are used as fixators and implants. Metal alloys remain in the tissues, are stable and do not allow their remodeling. Materials for biological application are expected to be non-toxic, biocompatible and meet physical and chemical characteristics such as strength, flexibility, elastic deformation and purity, suitable for different tissues, undergo biointegration inducing remodeling of the implant area. There are no materials that meet all the specifications of an ideal fabric substitute. The organic matrix composites used for biological applications are mostly protein derivatives such as collagen from different animal sources. These products are biologically active and can lead to immune rejection responses. Solution
O invento é um compósito cuja matriz é um polissacarídeo e o reforço é um composto de origem inorgânica (hidróxido de cálcio, hidroxiapatita e fosfato de cálcio). O reforço foi utilizado com a finalidade de associar uma indução bioativa no compósito, específica para o tecido ósseo. O reforço foi utilizado em concentrações diferentes em relação a matriz, para obtenção de compósitos com resistência a ruptura e diferentes índices de deformação elástica adequados as aplicações especificas de osteofixação, preenchimento de defeitos críticos, osteoindução, osteocondução e osteorepa ração. O reforço pode ser o hidróxido de cálcio, o hidroxiapatita ou o fosfato de cálcio, ou uma combinação dois a dois destes em diferentes proporções, ou ainda, pode-se usar, os três reforços combinados em diferentes proporções. The invention is a composite whose matrix is a polysaccharide and the reinforcement is a compound of inorganic origin (calcium hydroxide, hydroxyapatite and calcium phosphate). The reinforcement was used to associate a bioactive induction in the composite, specific to bone tissue. The reinforcement was used in different concentrations in relation to the matrix, to obtain composites with rupture resistance and different elastic deformation indices suitable to the specific applications of osteofixation, critical defects filling, osteoinduction, osteoconduction and osteorepation. The reinforcement may be calcium hydroxide, hydroxyapatite or calcium phosphate, or a two to two combination of these in different proportions, or the three reinforcements combined in different proportions may be used.
O biopolímero deve ser emulsificado para formar a matriz básica com concentrações diferentes para a adição de um dos reforços. A dispersão dos componentes deve ser feita por agitação. O excesso de água deve ser retirado o que resultará numa pasta que poderá ser modelada e desidratada. A massa resultante é um compósito modelável, resistente a ruptura e elasticamente deformável. Como exemplo de aplicação da invenção fez-se as seguintes experiências: A matriz referente a estas experiências foi de origem biológica, composta integralmente de açúcares e ácido glicurônico, componentes orgânicos encontrados como ativos metabólicos nos seres vivos, inclusive no homem. A matriz orgânica é um polissacarídeo constituído de açúcares de fontes naturais que não desperta resposta imunológica de rejeição como os derivados protéicos. O expolissacarideo bacteriano foi obtido com base no processo de produção descrito nos documentos PI9603700-8; PI0301912-8 e PI0504376-0. O biopolímero foi emulsificado a partir de uma suspensões em peso volume de lg do biopolímero para 50 a 150mL de água, formando a matriz básica com concentrações diferentes para a adição específica de um ou da associação do reforço nas concentrações entre 0,01 a 3% em relação a matriz. No caso, foram feitas experiências com hidróxido de cálcio e fosfato de cálcio. A dispersão dos componentes foi feita por agitação contínua por 30 minutos. O excesso de água foi retirado por meio de filtração. A pasta resultante foi modelada por extrusão a frio e compressão entre placas. Depois a massa foi desidratadas em ambiente livre de partículas em suspensão. A massa resultante é um compósito atóxico, bioativo, biocompativel, modelável, resistente a ruptura e elasticamente deformável. Em estudo "in vitro", o produto a que se refere a presente invenção apresentou em sua superfície a deposição de fosfato de cálcio, que se constitui num precursor da hidroxiapatita, material orgânico presente em 90% do tecido ósseo. Desta forma, o uso de um produto natural, biodegradável, obtido de matéria prima proveniente de fonte renovável como compósitos poliméricos apatita-orgânicos é um atrativo de vários métodos de fabricação de biomateriais como remodelador ósseo. The biopolymer must be emulsified to form the basic matrix at different concentrations for the addition of one of the reinforcements. Dispersion of components should be by agitation. Excess water should be removed which will result in a paste that can be shaped and dehydrated. The resulting mass is a resilient, resilient and elastically deformable composite. As an example of application of the invention the following experiments were performed: The matrix relating to these experiments was of biological origin, composed entirely of sugars and glucuronic acid, organic components found as metabolic actives in living beings, including man. Organic matrix is a polysaccharide consisting of sugars from natural sources that does not elicit an immune response of rejection like protein derivatives. Bacterial expolysaccharide was obtained based on the production process described in PI9603700-8; PI0301912-8 and PI0504376-0. The biopolymer was emulsified from a 1g volume weight suspensions of the biopolymer to 50 to 150mL of water, forming the base matrix at different concentrations for the specific addition of one or combination of reinforcement at concentrations of 0.01 to 3%. relative to the matrix. At the In this case, experiments were performed with calcium hydroxide and calcium phosphate. Dispersion of the components was by continuous stirring for 30 minutes. Excess water was removed by filtration. The resulting paste was modeled by cold extrusion and compression between plates. Then the dough was dehydrated in a particle free environment. The resulting mass is a non-toxic, bioactive, biocompatible, moldable, tear-resistant and elastically deformable composite. In an "in vitro" study, the product to which the present invention relates exhibited calcium phosphate deposition on its surface, which is a precursor of hydroxyapatite, an organic material present in 90% of bone tissue. Thus, the use of a biodegradable natural product obtained from raw material from renewable sources as apatite-organic polymer composites is an attraction of various methods of manufacturing biomaterials as bone remodeling.
Sumário summary
O invento refere-se ao desenvolvimento de um compósito bioativo, cuja matriz polimérica é composta de polissacarídeo. Como reforço utiliza-se derivados de cálcio como hidróxido de cálcio, hidróxido apatita, fosfato de cálcio com a finalidade de obtenção de compósitos bioativos com especificidade para o tecido ósseo. O reforço foi utilizado em concentrações diferentes em relação a matriz para obtenção de compósitos modeláveis, com resistência à ruptura e com diferentes índices de deformação elástica adequados as aplicações especificas de osteofixação, osteorepa ração, osteoindução e osteocondução para o tratamento de lesões do tecido ósseo com perda de substância incluindo defeitos críticos. The invention relates to the development of a bioactive composite whose polymeric matrix is composed of polysaccharide. As reinforcement, calcium derivatives such as calcium hydroxide, apatite hydroxide, calcium phosphate are used to obtain bioactive composites with specificity for bone tissue. The reinforcement was used at different concentrations in relation to the matrix to obtain modelable composites, with resistance to rupture and with different elastic deformation indices suitable to the specific applications of osteofixation, osteorepation, osteoinduction and osteoconduction for the treatment of bone tissue injuries. loss of substance including critical defects.
Descrição Detalhada O invento é um compósito cuja matriz é um polissacarídeo e o reforço é um composto de origem inorgânica (hidróxido de cálcio, hidroxiapatita e fosfato de cálcio). O reforço foi utilizado com a finalidade de associar uma indução bioativa no compósito, específica para o tecido ósseo. O reforço foi utilizado em concentrações diferentes em relação a matriz, para obtenção de compósitos com resistência a ruptura e diferentes índices de deformação elástica adequados as aplicações especificas de osteofixação, preenchimento de defeitos críticos, osteoindução, osteocondução e osteorepa ração. Detailed Description The invention is a composite whose matrix is a polysaccharide and the reinforcement is a compound of inorganic origin (calcium hydroxide, hydroxyapatite and calcium phosphate). The reinforcement was used to associate a bioactive induction in the composite, specific to for bone tissue. The reinforcement was used in different concentrations in relation to the matrix, to obtain composites with rupture resistance and different elastic deformation indices suitable to the specific applications of osteofixation, critical defects filling, osteoinduction, osteoconduction and osteorepation.
O biopolímero deve ser emulsificado para formar a matriz básica com concentrações diferentes para a adição de um dos reforços. A dispersão dos componentes deve ser feita por agitação. O excesso de água deve ser retirado o que resultará numa pasta que poderá ser modelada e desidratada. A massa resultante é um compósito modelável, resistente a ruptura e elasticamente deformável. The biopolymer must be emulsified to form the basic matrix at different concentrations for the addition of one of the reinforcements. Dispersion of components should be by agitation. Excess water should be removed which will result in a paste that can be shaped and dehydrated. The resulting mass is a resilient, resilient and elastically deformable composite.
Como exemplo de aplicação da invenção fez-se as seguintes experiências: A matriz referente a estas experiências é de origem biológica, composta integralmente de açúcares e ácido glicurônico, componentes orgânicos encontrados como ativos metabólicos nos seres vivos, inclusive no homem. A matriz orgânica é um polissacarídeo constituído de açúcares de fontes naturais que não desperta resposta imunológica de rejeição como os derivados protéicos. O expolissacarideo bacteriano foi obtido com base no processo de produção descrito nos documentos PI9603700-8; PI0301912-8 e PI0504376-0. O biopolímero foi emulsificado a partir de uma suspensões em peso volume de lg do biopolímero para 50 a 150mL de água, formando a matriz básica com concentrações diferentes e a adição de um ou dos reforços ou de sua associação na concentração de 0,01 a 3,0% da matriz. No caso, foram feitas experiências com hidróxido de cálcio e fosfato de cálcio. A dispersão dos componentes foi feita por agitação contínua por 30 minutos. O excesso de água foi retirado por meio de filtração. A pasta resultante foi modelada por extrusão a frio e compressão entre placas. Depois a massa foi desidratadas em ambiente seguro com baixo nível de partículas em suspensão. A massa resultante é um compósito atóxico, bioativo, biocompativel, modelável, resistente a ruptura e elasticamente deformável. Em estudo nin vitro", o produto a que se refere a presente invenção apresentou em sua superfície a deposição de fosfato de cálcio, que se constitui num precursor da hidroxiapatita, material orgânico presente em 90% do tecido ósseo. Desta forma, o uso de um produto natural, biodegradável, obtido de matéria prima proveniente de fonte renovável como compósitos poliméricos apatita-orgânicos é um atrativo de vários métodos de fabricação de biomateriais como remodelador ósseo. As an example of application of the invention the following experiments were made: The matrix of these experiments is of biological origin, composed entirely of sugars and glucuronic acid, organic components found as metabolic actives in living beings, including man. Organic matrix is a polysaccharide consisting of sugars from natural sources that does not elicit an immune response of rejection like protein derivatives. Bacterial expolysaccharide was obtained based on the production process described in PI9603700-8; PI0301912-8 and PI0504376-0. The biopolymer was emulsified from a 1g volume weight suspensions of the biopolymer to 50 to 150mL of water, forming the base matrix at different concentrations and the addition of one or the reinforcements or their association at a concentration of 0.01 to 3. , 0% of the matrix. In this case, experiments were performed with calcium hydroxide and calcium phosphate. Dispersion of the components was by continuous stirring for 30 minutes. Excess water was removed by filtration. The resulting paste was modeled by cold extrusion and compression between plates. Then the dough was dehydrated in a safe environment with low level of particulate matter. The resulting mass is a non-toxic, bioactive, biocompatible, moldable, tear-resistant and elastically deformable composite. In a non- in vitro study, "the product to which the present invention relates exhibited calcium phosphate deposition on its surface, which is a precursor of hydroxyapatite, an organic material present in 90% of bone tissue. A natural, biodegradable product obtained from raw materials from renewable sources such as apatite-organic polymer composites is an attraction of various methods of manufacturing biomaterials as bone remodeling.

Claims

REIVINDICAÇÕES
1. COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS constituído por uma matriz orgânica e reforços inorgânicos caracterizado pela matriz ser polimérica ser adicionada de reforço e o reforço ser um derivado de cálcio. 1. BIOACTIVE BONE REPAIR COMPOSITE consisting of an organic matrix and inorganic reinforcements characterized in that the matrix is polymeric is added reinforcement and the reinforcement is a calcium derivative.
2. COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1 caracterizado pela dita matriz ser um polissacarídeo. BIOACTIVE BONE REPAIR COMPOSITE according to claim 1, characterized in that said matrix is a polysaccharide.
3. COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 2 caracterizado pelo dito polissacarídeo ser um expolissacarídeo. BIOACTIVE BONE REPAIR COMPOSITE according to claim 2, characterized in that said polysaccharide is an expolysaccharide.
4. COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1 , 2 ou 3 caracterizado pelo dito reforço ser hidróxido de cálcio ou fosfato de cálcio ou hidroxiapatita. BIOACTIVE BONE REPAIR COMPOSITE according to claim 1, 2 or 3, characterized in that said reinforcement is calcium hydroxide or calcium phosphate or hydroxyapatite.
5. COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1 , 2 ou 3 caracterizado pelo dito reforço ser qualquer mistura entre hidróxido de cálcio, fosfato de cálcio e hidroxiapatita, combinados dois a dois ou os três em conjunto. BIOACTIVE BONE REPAIR COMPOSITE according to Claim 1, 2 or 3, characterized in that said reinforcement is any mixture of calcium hydroxide, calcium phosphate and hydroxyapatite, combined two by two or all three together.
6. COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1 , 2, 3, 4 ou 5 caracterizado pelo dito reforço associar uma indução bioativa, específica para o tecido ósseo, na dita matriz. BIOACTIVE BONE REPAIR COMPOSITE according to claim 1, 2, 3, 4 or 5 characterized in that said reinforcement associates a bone tissue specific bioactive induction in said matrix.
7. PROCESSO DE OBTENÇÃO DE COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS para obter o compósito conforme reivindicações 1, 2,7. BIOACTIVE COMPOSITE PROCESS FOR BONE REPAIR to obtain the composite according to claims 1, 2,
3. 4, 5 ou 6 caracterizado pela matriz orgânica ser emulsificada com concentrações diferentes dos reforços inorgânicos, pela dispersão dos componentes ser feita por agitação, pelo excesso de água ser retirado e finalmente pela pasta ser modelada e desidratada para uso. 3. 4, 5 or 6 characterized in that the organic matrix is emulsified with different concentrations of inorganic reinforcements, dispersion of the components is by agitation, excess water is removed and finally the paste is shaped and dehydrated for use.
8. PROCESSO DE OBTENÇÃO DE COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 7 caracterizado pela dita matriz orgânica ser obtida com base no processo de produção descrito nos documentos PI9603700-8; PI0301912-8 e PI0504376-0. BIOACTIVE COMPOSITE PROCESS FOR BONE REPAIR according to claim 7, characterized in that said organic matrix is obtained based on the production process described in PI9603700-8; PI0301912-8 and PI0504376-0.
9. PROCESSO DE OBTENÇÃO DE COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 7 ou 8 caracterizado pela dita matriz ser emulsificada a partir de uma suspensões em peso volume de lg de biopolímero para 50 a 150mL de água. BIOACTIVE COMPOSITE PROCESS FOR BONE REPAIR according to claim 7 or 8, characterized in that The matrix is emulsified from a 1 g volume by weight suspensions of biopolymer to 50 to 150 ml of water.
10. PROCESSO DE OBTENÇÃO DE COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 7, 8 ou 9 caracterizado pelo compósito ser formado pela adição do reforço à matriz em concentrações diferentes variando de 0,01 a 3%. BIOACTIVE COMPOSITE PROCESS FOR BONE REPAIR according to claim 7, 8 or 9 characterized in that the composite is formed by adding the reinforcement to the matrix at different concentrations ranging from 0.01 to 3%.
1 1. PROCESSO DE OBTENÇÃO DE COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 7, 8, 9 ou 10 caracterizado pelo reforço ser o hidróxido de cálcio ou o fosfato de cálcio ou hidroxiapatita usados de forma isolada ou combinada. BIOACTIVE COMPOSITE PROCESS FOR BONE REPAIR according to claim 7, 8, 9 or 10, characterized in that the reinforcement is calcium hydroxide or calcium phosphate or hydroxyapatite used alone or in combination.
12. PROCESSO DE OBTENÇÃO DE COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 7, 8, 9, 10 ou 1 1 caracterizado pela dispersão dos componentes ser feita por agitação contínua por 30 minutos. BIOACTIVE COMPOSITE PROCESS FOR BONE REPAIR according to claim 7, 8, 9, 10 or 11 characterized in that the dispersion of the components is by continuous stirring for 30 minutes.
13. PROCESSO DE OBTENÇÃO DE COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 7, 8, 9, 10, 1 1 ou 12 caracterizado pela massa resultante ser desidratadas em ambiente livre de partículas em suspensão. BIOACTIVE COMPOSITE PROCESS FOR BONE REPAIR according to claim 7, 8, 9, 10, 11 or 12 characterized in that the resulting mass is dehydrated in an environment free of particulate matter.
14. USO DO COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1 , 2, 3, 4, 5, 6 ou obtido do processo conforme reivindicação 7, 8, 9, 10, 1 1 , 12 ou 13 como fixador de tecidos ósseos, preenchimento de defeitos críticos dos tecidos ósseos, osteocondução ou osteoindução. Use of the BIOACTIVE COMPOSITE FOR BONE REPAIR according to claim 1, 2, 3, 4, 5, 6 or obtained from the process according to claim 7, 8, 9, 10, 11, 13 or 13 as a bone tissue fixative, filler critical bone tissue defects, osteoconduction or osteoinduction.
15. USO DO COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1 , 2, 3, 4, 5, 6 ou obtido do processo conforme reivindicação 7, 8, 9, 10, 1 1 , 12 ou 13 como base para liberação controlada de medicamentos e nanodispositivos. Use of the BIOACTIVE COMPOSITE FOR BONE REPAIR according to claim 1, 2, 3, 4, 5, 6 or obtained from the process according to claim 7, 8, 9, 10, 1 1, 12 or 13 as a basis for controlled release of drugs and nanodevices.
16. USO DO COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1, 2, 3, 4, 5, 6 ou obtido do processo conforme reivindicação 7, 8, 9, 10, 1 1, 12 ou 13 substitutivos ósseos com função de condução e indução de tecido. Use of the BIOACTIVE COMPOSITE FOR BONE REPAIR according to claim 1, 2, 3, 4, 5, 6 or obtained from the process according to claim 7, 8, 9, 10, 1 1, 12 or 13 bone substitutes with conduction and induction function of fabric.
17. USO DO COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS conforme reivindicação 1, 2, 3, 4, 5, 6 ou obtido do processo conforme reivindicação 7, 8, 9, 10, 1 1, 12 ou 13 como pinos fixadores de lesões do tecido ósseo ou usinados no modelo de parafusos com a mesma função e aplicação. Use of the BIOACTIVE COMPOSITE FOR BONE REPAIR according to claim 1, 2, 3, 4, 5, 6 or obtained from the process according to claim 7, 8, 9, 10, 1 1, 12 or 13 as bone tissue injury fixation pins or machined on the bolt model with the same function and application.
18. USO DO COMPÓSITO BIOATIVO PARA REPAROS ÓSSEOS, conforme reivindicação 1, 2, 3, 4, 5, 6 ou obtido do processo conforme reivindicação 7, 8, 9, 10, 1 1 , 12 ou 13, em forma de laminados para correção de defeitos críticos de ossos planos ou como placas fixadoras. Use of the BIOACTIVE COMPOSITE FOR BONE REPAIR according to claim 1, 2, 3, 4, 5, 6 or obtained from the process according to claim 7, 8, 9, 10, 11, 12 or 13 in the form of correction laminates critical defects of flat bones or as fixation plates.
PCT/BR2010/000144 2009-04-22 2010-04-15 Bioactive composite for bone repair WO2010121341A2 (en)

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